Potent antihyperglycaemic property of a new imidazoline derivative S-22068 (PMS 847) in a rat model of NIDDM (original) (raw)

1998, British Journal of Pharmacology

Recent data suggest that some imidazoline derivatives can lower plasma glucose in experimental animal models of diabetes. We studied the activity of an imidazoline S-22068, in rat model of non-insulin-dependent diabetes mellitus (NIDDM) produced with a low dose of streptozotocin (35 mg kg−1, i.v.) in the adult.The respective increase over basal value in glucose (ΔG) and insulin (ΔI), and the rate of glucose disappearance (K), were measured during a 30 min intravenous glucose tolerance test. After an intraperitoneal injection of S-22068 (24 mg kg−1), ΔG (mM min −1) was decreased (91.67±5.83 vs 120.5±3.65; P<0.001), whereas K was increased (1.74±0.09 vs 1.18±0.05; P<0.001). Although insulinaemia was increased at time-point 0 of the test, ΔI was unchanged.During oral glucose tolerance tests (OGTT), S-22068 (24 mg kg−1, p.o.) improved glucose tolerance, and its efficiency was potentiated after chronic treatment (15 days). Basal glycaemia was unaffected by the treatment. Under the same conditions, a higher dose of S-22068 (40 mg kg−1) further improved glucose tolerance without causing hypoglycaemia.Binding experiments revealed that S-22068 displays no affinity for either adrenoceptors or the two imidazoline receptors I1 or I2.These results demonstrate that S-22068 improves glucose tolerance without causing hypoglycaemia. Thus S-22068 represents a new potential option in the treatment of NIDDM.Recent data suggest that some imidazoline derivatives can lower plasma glucose in experimental animal models of diabetes. We studied the activity of an imidazoline S-22068, in rat model of non-insulin-dependent diabetes mellitus (NIDDM) produced with a low dose of streptozotocin (35 mg kg−1, i.v.) in the adult.The respective increase over basal value in glucose (ΔG) and insulin (ΔI), and the rate of glucose disappearance (K), were measured during a 30 min intravenous glucose tolerance test. After an intraperitoneal injection of S-22068 (24 mg kg−1), ΔG (mM min −1) was decreased (91.67±5.83 vs 120.5±3.65; P<0.001), whereas K was increased (1.74±0.09 vs 1.18±0.05; P<0.001). Although insulinaemia was increased at time-point 0 of the test, ΔI was unchanged.During oral glucose tolerance tests (OGTT), S-22068 (24 mg kg−1, p.o.) improved glucose tolerance, and its efficiency was potentiated after chronic treatment (15 days). Basal glycaemia was unaffected by the treatment. Under the same conditions, a higher dose of S-22068 (40 mg kg−1) further improved glucose tolerance without causing hypoglycaemia.Binding experiments revealed that S-22068 displays no affinity for either adrenoceptors or the two imidazoline receptors I1 or I2.These results demonstrate that S-22068 improves glucose tolerance without causing hypoglycaemia. Thus S-22068 represents a new potential option in the treatment of NIDDM.British Journal of Pharmacology (1998) 124, 1591–1596; doi:10.1038/sj.bjp.0701989